Browsing by Person "Pickles, A."

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CMIP and ATP2C2 Modulate Phonological Short-Term Memory in Language Impairment
(2009-08-14) Newbury, D. F.; Winchester, Laura; Addis, L.; Paracchini, Silvia; Buckingham, Lyn-Louise; Clark, Ann; Cohen, W.; Cowie, H.; Dworzynski, Katharina; Everitt, Andrea; Goodyer, I. M.; Hennessy, E.; Kindley, A. D.; Miller, Laura L.; Nasir, J.; O'Hare, Anne; Shaw, D.; Simkin, Z.; Simonoff, E.; Slonims, V.; Watson, Jocelynne; Ragoussis, Jiannis; Fisher, S. E.; Seckl, J.; Helms, P. J.; Bolton, P. F.; Pickles, A.; Conti-Ramsden, G.; Baird, G.; Bishop, DVM; Monaco, A. P.
Specific language impairment (SLI) is a common developmental disorder characterized by difficulties in language acquisition despite otherwise normal development and in the absence of any obvious explanatory factors. We performed a high-density screen of SLI1, a region of chromosome 16q that shows highly significant and consistent linkage to nonword repetition, a measure of phonological short-term memory that is commonly impaired in SLI. Using two independent language-impaired samples, one family-based (211 families) and another selected from a population cohort on the basis of extreme language measures (490 cases), we detected association to two genes in the SLI1 region: that encoding c-maf-inducing protein (CMIP, minP = 5.5 10-7 at rs6564903) and that encoding calcium-transporting ATPase, type2C, member2 (ATP2C2, minP = 2.0 10-5 at rs11860694). Regression modeling indicated that each of these loci exerts an independent effect upon nonword repetition ability. Despite the consistent findings in language-impaired samples, investigation in a large unselected cohort (n = 3612) did not detect association. We therefore propose that variants in CMIP and ATP2C2 act to modulate phonological short-term memory primarily in the context of language impairment. As such, this investigation supports the hypothesis that some causes of language impairment are distinct from factors that influence normal language variation. This work therefore implicates CMIP and ATP2C2 in the etiology of SLI and provides molecular evidence for the importance of phonological short-term memory in language acquisition.
Genetic and phenotypic effects of phonological short-term memory and grammatical morphology in specific language impairment
(2008-06) Falcaro, M.; Pickles, A.; Newbury, D. F.; Addis, L.; Banfield, E.; Fisher, S. E.; Monaco, A. P.; Simkin, Z.; Conti-Ramsden, G.; Newbury, D. F.; Banfield, E.; Addis, L.; Cleak, J. D.; Cardon, L. R.; Merriden, M. J.; Goodyer, I. M.; Simonoff, E.; Bolton, P. F.; Slonims, V.; Baird, G.; Everitt, Andrea; Hennessy, E.; Shaw, D.; Helms, P. J.; Kindley, A. D.; Clark, Ann; Watson, Jocelynne; O'Hare, Anne; Seckl, J.; Cowie, H.; Cohen, W.; Nasir, J.; Bishop, DVM
Deficits in phonological short-term memory and aspects of verb grammar morphology have been proposed as phenotypic markers of specific language impairment (SLI) with the suggestion that these traits are likely to be under different genetic influences. This investigation in 300 first-degree relatives of 93 probands with SLI examined familial aggregation and genetic linkage of two measures thought to index these two traits, non-word repetition and tense marking. In particular, the involvement of chromosomes 16q and 19q was examined as previous studies found these two regions to be related to SLI. Results showed a strong association between relatives' and probands' scores on non-word repetition. In contrast, no association was found for tense marking when examined as a continuous measure. However, significant familial aggregation was found when tense marking was treated as a binary measure with a cut-off point of -1.5 SD, suggestive of the possibility that qualitative distinctions in the trait may be familial while quantitative variability may be more a consequence of non-familial factors. Linkage analyses supported previous findings of the SLI Consortium of linkage to chromosome 16q for phonological short-term memory and to chromosome 19q for expressive language. In addition, we report new findings that relate to the past tense phenotype. For the continuous measure, linkage was found on both chromosomes, but evidence was stronger on chromosome 19. For the binary measure, linkage was observed on chromosome 19 but not on chromosome 16. 2007 The Authors.